Gene expression profiling of primary breast carcinomas using arrays of candidate genes

Abstract

Method for molecular characterization of a carcinoma including: (i) detecting in tumor cells corresponding to breast tumor cells at least one polynucleotide selected from a first group determining expression level of the polynucleotide from the first group to differentiate a tumor in which a lymph node has been invaded by a tumor cell from a tumor in which a lymph node has not been invaded by a tumor cell; (ii) detecting in tumor cells corresponding to breast tumor cells at least one polynucleotide selected from a second group determining expression level of the polynucleotide from the second group to distinguish tumors sensitive to anthracycline from tumors insensitive to anthracycline; (iii) detecting in tumor cells corresponding to breast tumor cells at least one polynucleotide selected from a third group determining expression levels of the polynucleotide from the third group to classify good and poor prognosis primary breast tumors.

1 . A method for the molecular characterization of a carcinoma comprising the steps of:
 (i) detecting in tumor cells corresponding to breast tumor cells at least one polynucleotide selected from a first group comprising:
 EST T89980 (SEQ ID No: 16), 
 SOX 4 (SEQ ID No: 22, SEQ ID No: 23, SEQ ID No: 24), 
 ENPP2 (SEQ ID No: 39, SEQ ID No: 40, SEQ ID No.41), 
 MUC 1 (SEQ ID No: 57, SEQ ID No: 58), 
 GATA3 (SEQ ID No: 76, SEQ ID No: 77, SEQ ID No: 78), 
 TOP2B (SEQ ID No: 82, SEQ ID No: 83), 
 IL2RB (SEQ ID No: 97, SEQ ID No: 98, ID No: 99), 
 ERBB2 (SEQ ID No: 118, SEQ ID No: 119), 
 EGFR (SEQ ID No: 135, SEQ ID No: 136, SEQ ID No: 137), 
 THBS1 (SEQ ID No: 216, SEQ ID No: 217), 
 PPP2R2C (SEQ ID No: 238, SEQ ID No: 239), 
 ATF3 (SEQ ID No: 250, SEQ ID No: 251, SEQ ID No: 252), 
 KIAA1075 (SEQ ID No: 322, SEQ ID No: 323), 
 CDH1 (SEQ ID No: 326, SEQ ID No: 327, SEQ ID No: 328), 
 ZNF144 (SEQ ID No: 329, SEQ ID No: 330), 
 GSTP1 (SEQ ID No: 334, SEQ ID No: 335, SEQ ID No: 336), 
 CD44 (SEQ ID No: 374, SEQ ID No: 375, SEQ ID No: 376), 
 GZMA (SEQ ID No: 402, SEQ ID No: 403), 
 EST T80406 (SEQ ID No: 430), and 
 ESTs H30141 & H27466 (SEQ ID No: 438, SEQ ID No: 439) 
 determining the expression level of the at least one polynucleotide from the first group to differentiate a tumor in which a lymph node has been invaded by a tumor cell from a tumor in which a lymph node has not been invaded by a tumor cell; 
   (ii) detecting in tumor cells corresponding to breast tumor cells at least one polynucleotide selected from a second group comprising:
 SOX4 11 (SEQ ID No: 22, SEQ ID No: 23, SEQ ID No: 24), 
 CSF1 (SEQ ID No: 48, SEQ ID No: 49, SEQ ID No: 50), 
 VIL2 (SEQ ID No: 51, SEQ ID No: 52, SEQ ID No: 53), 
 IGF2 (SEQ ID No: 59, SEQ ID No: 60, SEQ ID No: 61), 
 KIAA0427 (SEQ ID No: 65, SEQ ID No: 66, SEQ ID No: 67), 
 MYC (SEQ ID No: 73, SEQ ID No: 74, SEQ ID No: 75), 
 GATA3 (SEQ ID No: 76, SEQ ID No: 77, SEQ ID No: 78), 
 TOP2B (SEQ ID No: 82, SEQ ID No: 83), 
 ERBB2 (SEQ ID No: 118, SEQ ID No: 119), 
 EGFR (SEQ ID No: 135, SEQ ID No: 136, SEQ ID No: 137), 
 CRABP2 (SEQ ID No 156, SEQ ID No: 157, SEQ ID No: 158), 
 GZMB 73 (SEQ ID No: 178, SEQ ID No: 179), 
 IGKC (SEQ ID No: 186), 
 ANG (SEQ ID No: 194, SEQ ID No: 195), 
 EFNA1 (SEQ ID No: 226, SEQ ID No: 227), 
 MYBL2 (SEQ ID No: 308, SEQ ID No: 309, SEQ ID No: 310), 
 CDH1 (SEQ ID No: 326, SEQ ID No: 327, SEQ ID No: 328), 
 MST1 (SEQ ID No: 331, SEQ ID No: 332, SEQ ID No: 333), 
 MYB (SEQ ID No: 354, SEQ ID No: 355), 
 XBP1 (SEQ ID No: 385, SEQ ID No: 386, SEQ ID No: 387), 
 SRF (SEQ ID No: 391, SEQ ID No: 392, SEQ ID No: 393), 
 SOX9 (SEQ ID No: 394, SEQ ID No: 395), and 
 ESTs H21879 & H21880 (SEQ ID No: 433, SEQ ID No: 434) 
 determining the expression level of the at least one polynucleotide from the second group to distinguish tumors sensitive to anthracycline from tumors insensitive to anthracycline; 
   (iii) detecting in tumor cells corresponding to breast tumor cells at least one polynucleotide selected from a third group comprising:
 CTSB (SEQ ID No: 30, SEQ ID No: 31), 
 VIL2 (SEQ ID No: 51, SEQ ID No: 52, SEQ ID No: 53), 
 MUC1 (SEQ ID No: 57, SEQ ID No: 58), 
 EMR1 (SEQ ID No: 62, SEQ ID No: 63, SEQ ID No: 64), 
 KIAA0427 (SEQ ID No: 65, SEQ ID No: 66, SEQ ID No: 67), 
 GATA3 (SEQ ID No: 76, SEQ ID No: 77, SEQ ID No: 78), 
 PRLR 39 (SEQ ID No: 94, SEQ ID No: 95, SEQ ID No: 96), 
 GATA3 (SEQ ID No: 100, SEQ ID No: 101, SEQ ID No: 78), 
 TC21 (SEQ ID No 106, SEQ ID No: 107, SEQ ID No: 108), 
 BCL2 (SEQ ID No: 115, SEQ ID No: 116, SEQ ID No: 117), 
 CRABP2 (SEQ ID No: 156, SEQ ID No: 157, SEQ ID No: 158), 
 ANG (SEQ ID No: 194, No: 195), 
 EGF (SEQ ID No: 199, SEQ ID No: 200), 
 THBS1 (SEQ ID No: 216, SEQ ID No: 217), 
 EDNRA (SEQ ID No: 228, SEQ ID No: 229), 
 SMARCA2 (SEQ ID No: 235, SEQ ID No: 236, SEQ ID No: 237), 
 ABCB1 (SEQ ID No: 257, SEQ ID No: 258), 
 BIRC4 (SEQ ID No: 273, SEQ ID No: 274), 
 DAP3 (SEQ ID No: 275, SEQ ID No: 276), 
 GNRH1 (SEQ ID No: 277, SEQ ID No: 278), 
 EST R97218 (SEQ ID No: 296, SEQ ID No: 297), 
 BS69 (SEQ ID No: 342, SEQ ID No: 343, SEQ ID No: 344), 
 MYB (SEQ ID No: 354, SEQ ID No: 355), 
 CTSB (SEQ ID No: 361, SEQ ID No: 31), 
 MLANA (SEQ ID No: 362, SEQ ID No: 363, SEQ ID No: 364), 
 APR-1 (SEQ ID No: 365, SEQ ID No: 366, SEQ ID No: 367), 
 CDKN3 (SEQ ID No: 377, SEQ ID No: 378, SEQ ID No: 379) 
 XBP1 (SEQ ID No: 385, SEQ ID No: 386, SEQ ID No: 387), 
 CDH15 (SEQ ID No: 396, SEQ ID No: 397, SEQ ID No: 398), 
 EST W73386 168 ests (SEQ 1D No: 401), 
 ILF1 (SEQ ID No: 406, SEQ ID No: 407, SEQ ID No: 408), 
 ARHGDIA (SEQ ID No: 409, SEQ ID No: 410, SEQ ID No: 411), 
 C4A (SEQ ID No: 412, SEQ ID No: 413), 
 ESR1 (SEQ ID No: 420, SEQ ID No: 421, SEQ ID No: 422), 
 PBX1 (SEQ ID No: 423, SEQ ID No: 424, SEQ ID No: 425), 
 GLI3 (SEQ ID No: 426, SEQ ID No: 427, SEQ ID No: 428), 
 ESTs H24628 & H24592 (SEQ ID No: 435, SEQ ID No: 436), and 
 EST H28056 (SEQ ID No: 437) 
 determining the expression levels of the at least one polynucleotide from the third group to classify good and poor prognosis primary breast tumors. 
   
     
     
         2 . The method of  claim 1 , wherein the step (i) of differentiating a tumor in which a lymph node has been invaded by a tumor cell from a tumor in which a lymph node has not been invaded by a tumor cell is done by detecting at least one ERBB2 polynucleotide having the sequence SEQ ID No: 119 in tumor cells corresponding to breast tumor cells. 
     
     
         3 . The method of  claim 2 , wherein ERBB2 (SEQ ID No: 119) expression is strongly correlated with the lymph node status (p≦0.0001) 
     
     
         4 . The method of  claim 1 , wherein the step (ii) of distinguishing tumors sensitive to anthracycline from tumors insensitive to anthracycline is done by detecting at least one MYBL2 polynucleotide having the sequence SEQ ID No: 310 in tumor cells corresponding to breast tumor cells. 
     
     
         5 . The method of  claim 1 , wherein the step (iii) of classifying good and poor prognosis primary breast tumors is done by detecting at least one BCL2 polynucleotide having the sequence SEQ ID No: 117 in tumor cells corresponding to breast tumor cells. 
     
     
         6 . The method of  claim 1 , wherein said method further comprises the step (iv) of detecting at least one further polynucleotide which is underexpressed or overexpressed in breast tumor cells, which at least one further polynucleotide is selected in the group comprising any of the sequences SEQ ID Nos: 1-468 or the complement thereof. 
     
     
         7 . The method of  claim 6 , wherein the step (iv) corresponds to the detection of at least one GRB7 polynucleotide having the sequence SEQ ID No: 81 in tumor cells corresponding to breast tumor cells. 
     
     
         8 . The method of  claim 1 , wherein said method uses a polynucleotide library. 
     
     
         9 . The method of  claim 8 , wherein said polynucleotide library is immobilized on a solid support in order to form a polynucleotide array. 
     
     
         10 . The method of  claim 9 , wherein the solid support is selected from the group consisting of a nylon membrane, glass slide, glass beads, or a silicon chip.